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- Christophersen, Nicolaj, et al.
(författare)
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Induction of dopaminergic neurons from growth factor expanded neural stem/progenitor cell cultures derived from human first trimester forebrain.
- 2006
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230 .- 1873-2747. ; 70:4-6, s. 457-466
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Tidskriftsartikel (refereegranskat)abstract
- Multipotent stem/progenitor cells derived from human first trimester forebrain can be expanded as free-floating aggregates, so called neurospheres. These cells can differentiate into neurons, astrocytes and oligodendrocytes. In vitro differentiation protocols normally yield γ-aminobutyric acid-immunoreactive neurons, whereas only few tyrosine hydroxylase (TH) expressing neurons are found. The present report describes conditions under which 4–10% of the cells in the culture become TH immunoreactive (ir) neurons within 24 h. Factors including acidic fibroblast growth factor (aFGF) in combination with agents that increase intracellular cyclic AMP and activate protein kinase C, in addition to a substrate that promotes neuronal differentiation appear critical for efficient TH induction. The cells remain THir after trypsinization and replating, even when their subsequent culturing takes place in the absence of inducing factors. Consistent with a dopaminergic phenotype, mRNAs encoding aromatic acid decarboxylase, but not dopamine-β-hydroxylase were detected by quantitative real time RT-PCR. Ten weeks after the cells had been grafted into the striatum of adult rats with unilateral nigrostriatal lesions, only very few of the surviving human neurons expressed TH. Our data suggest that a significant proportion of expandable human neural progenitors can differentiate into TH-expressing cells in vitro and that they could be useful for drug and gene discovery. Additional experiments, however, are required to improve the survival and phenotypic stability of these cells before they can be considered useful for cell replacement therapy in Parkinson's disease.
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- Dekundy, A, et al.
(författare)
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Effects of group I metabotropic glutamate receptors blockade in experimental models of Parkinson's disease
- 2006
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 69:3, s. 318-326
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Tidskriftsartikel (refereegranskat)abstract
- The present study was devoted to investigate the effects of the metabotropic glutamate receptor(mGluR)5 antagonist [(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) and the mGluR1 antagonist, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate (EMQMCM), in animal studies indicative of antiparkinsonian-like activity such as haloperidol-induced catalepsy, hypoactivity in open field following haloperidol, and rotation in rats with unilateral 6-hydroxydopamine(OHDA)-induced lesions of the midbrain dopaminergic system (alone and in combination with L-DOPA). Moreover, antidyskinetic activity of different mGluR ligands was evaluated in the rat model of L-DOPA-induced dyskinesia. Both MTEP (5 mg/kg) and EMQMCM (4 mg/kg) slightly inhibited haloperidol (0.5 mg/kg)-induced catalepsy. However, neither substance reversed the hypoactivity produced by haloperidol (0.2 mg/kg). Although MTEP and not produce significant turning, it inhibited contralateral rotations after L-DOPA (at 5 mg/kg) and alleviated L-DOPA-induced dyskinesia (at 2.5 and 5 mg/kg) in 6-OHDA-lesioned rats. In contrast, mGluR1 antagonists EMQMCM and RS-1-aminoindan-1,5-dicarboxylic acid (AIDA) failed to modify L-DOPA-induced dyskinesia. The results of the present study suggest that either subtype of group I of mGluRs may be involved in the pathologically altered circuitry in the basal ganglia. However, the equivocal results do not strongly support the hypothesis that mGluR1 and mGluR5 antagonists may be beneficial in the symptomatic treatment of Parkinson's disease. However, mGluR5 antagonists may prove useful for the symptomatic treatment Of L-DOPA-induced dyskinesia. (c) 2006 Elsevier Inc. All rights reserved.
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- Edin, Benoni B, et al.
(författare)
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Bio-inspired sensorization of a biomechatronic robot hand for the grasp-and-lift task.
- 2008
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230 .- 1873-2747. ; 75:6, s. 785-95
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Tidskriftsartikel (refereegranskat)abstract
- It has been concluded from numerous neurophysiological studies that humans rely on detecting discrete mechanical events that occur when grasping, lifting and replacing an object, i.e., during a prototypical manipulation task. Such events represent transitions between phases of the evolving manipulation task such as object contact, lift-off, etc., and appear to provide critical information required for the sequential control of the task as well as for corrections and parameterization of the task. We have sensorized a biomechatronic anthropomorphic hand with the goal to detect such mechanical transients. The developed sensors were designed to specifically provide the information about task-relevant discrete events rather than to mimic their biological counterparts. To accomplish this we have developed (1) a contact sensor that can be applied to the surface of the robotic fingers and that show a sensitivity to indentation and a spatial resolution comparable to that of the human glabrous skin, and (2) a sensitive low-noise three-axial force sensor that was embedded in the robotic fingertips and showed a frequency response covering the range observed in biological tactile sensors. We describe the design and fabrication of these sensors, their sensory properties and show representative recordings from the sensors during grasp-and-lift tasks. We show how the combined use of the two sensors is able to provide information about crucial mechanical events during such tasks. We discuss the importance of the sensorized hand as a test bed for low-level grasp controllers and for the development of functional sensory feedback from prosthetic devices.
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- Grafström, Gustav, et al.
(författare)
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Histopathological examinations of rat brains after long-term exposure to GSM-900 mobile phone radiation.
- 2008
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 77, s. 257-263
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Tidskriftsartikel (refereegranskat)abstract
- In order to mimic the real life situation, with often life-long exposure to the electromagnetic fields emitted by mobile phones, we have investigated in a rat model the effects of repeated exposures under a long period to Global System for Mobile Communication-900MHz (GSM-900) radiation. Out of a total of 56 rats, 32 were exposed once weekly in a 2-h period, for totally 55 weeks, at different average whole-body specific absorption rates (SAR) (of in average 0.6 and 60mW/kg at the initiation of the experimental period). The animals were exposed in a transverse electromagnetic transmission line chamber (TEM-cell) to radiation emitted by a GSM-900 test phone. Sixteen animals were sham exposed and eight animals were cage controls, which never left the animal house. After behavioural tests, 5-7 weeks after the last exposure, the brains were evaluated for histopathological alterations such as albumin extravasation, dark neurons, lipofuscin aggregation and signs of cytoskeletal and neuritic neuronal changes of the type seen in human ageing. In this study, no significant alteration of any these histopathological parameters was found, when comparing the GSM exposed animals to the sham exposed controls.
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- Grealish, Shane, et al.
(författare)
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Unilateral axonal or terminal injection of 6-hydroxydopamine causes rapid-onset nigrostriatal degeneration and contralateral motor impairments in the rat.
- 2008
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 77, s. 312-319
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Tidskriftsartikel (refereegranskat)abstract
- Unilateral injection of the catecholamine neurotoxin 6-hydroxydopamine into the axons or terminals of the nigrostriatal pathway is commonly used to model Parkinson's disease in experimental animals. Although the terminal lesion paradigm is considered to induce a more progressive lesion when compared to the axonal lesion, few studies have directly compared the early time-course for lesion development in these two models. Thus, this experiment is sought to establish the temporal pattern of nigrostriatal degeneration and emergence of contralateral motor impairment in these models. Young adult male Lister Hooded rats were used. After baseline testing on a battery of spontaneous motor tests, standard stereotaxic techniques were used to inject 6-hydroxydopamine into the nigrostriatal axons or terminals at the level of the medial forebrain bundle or striatum respectively. From the day after lesion surgery, a subset of the rats was tested for motor performance, while another subset was used for immunohistochemical analysis. Quantitative tyrosine hydroxylase immunohistochemistry revealed that although both lesions caused a similar temporal pattern of immunopositive cell loss from the substantia nigra, the terminal lesion caused a more rapid loss of immunopositive terminals from the striatum. Despite these differences in striatal dopaminergic deafferentation, both lesion types caused a profound loss of contralateral motor function from the first day after lesion surgery. These findings illustrate the rapidity of the neuropathological and behavioural consequences of either axonal or terminal injection of 6-hydroxydopamine into the nigrostriatal pathway, and further highlight the need for a more progressive model of human Parkinson's disease.
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- Hagell, Peter, et al.
(författare)
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Dyskinesias and dopamine cell replacement in Parkinson's disease: a clinical perspective.
- 2005
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Ingår i: Brain Research Bulletin. - : Elsevier BV. - 0361-9230. ; 68:1-2, s. 4-15
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Tidskriftsartikel (refereegranskat)abstract
- Both increased and decreased dyskinesias have been reported from open label clinical trials of transplantation of human embryonic dopamine rich tissue in Parkinson's disease patients. In the first double-blind clinical transplantation trial, 15% of the grafted patients developed severe postoperative dyskinesias in the “off” phase. Since then, postoperative off-medication dyskinesias have been reported from two additional series of grafted patients. However, such dyskinesias are probably not a novel phenomenon. These dyskinesias have shown a different temporal development postoperatively compared to the antiparkinsonian graft effects, and no significant relationship with the magnitude of graft-derived dopaminergic reinnervation or symptomatic relief. However, positron emission tomography studies have indicated that an unbalanced putaminal dopaminergic function may contribute to this postoperative complication. While there is little doubt that intrastriatal grafts can induce dyskinesias, these appear to differ from common drug-induced dyskinesias. The term graft-induced dyskinesias (GID) is therefore suggested to more clearly identify this complication. While GID bear some phenomenological resemblance to biphasic drug induced dyskinesias, the mechanism(s) behind this complication remains obscure. Available data are scarce but allow for hypotheses to be generated that could (and should) be addressed in experimental animals.
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